Helicobacter pylori (H. pylori) infects over half of the world's population and is associated with multiple disease states ranging from gastritis and duodenal ulcer to gastric cancer and lymphomas. The mechanisms leading from infection to malignancy are not clearly established, but are prominently associated with the type of inflammatory response to the bacteria. In addition to inducing an antibody response, H. pylori causes a T cell response which initially appears to be a Th1 type with the production of IL2, IFNgamma, and TNFalpha and the development of gastritis. The type of gastritis has been divided into two major categories by its histologic appearance, non-atrophic gastritis (NAG), generally associated with duodenal ulcer disease, and Multi-focal atrophic gastritis (MAG), associated with gastric ulcers, epithelial dysplasia and gastric cancer. Most of the previous work has studied the immune response on patients with NAG, while little is known on patients with MAG. Our preliminary data comparing both groups of patients shows an increased infiltration by B cells and an enhanced expression of HLA-DR expression in patients with NAG, which markedly decreases in patients with MAG. In contrast the peripheral blood lymphocytes of patients with MAG show a significantly increased production of IFNgamma, IL5 and IL10 after stimulation with H. pylori antigens. However, our data also shows that H. pylori can impair the T cell response by diminishing the proliferation to mitogens, altering the expression of signal transduction proteins and, in patients with MAG, increasing the production of arginase, an enzyme known to diminish the T cell response. Therefore our hypothesis is that the immune response to H. pylori antigens differs in patients with NAG and MAG and therefore plays a central role in determining the type of gastritis developed by the host and its possible progression to gastric malignancy. To test this hypothesis we have developed the following specific aims: 1. To Compare the local inflammatory response in the gastric mucosa of patients with Non-atrophic antral gastritis (NAG) and patients with Multi-focal atrophic gastritis (MAG) using histopathology, immunohistochemistry and in situ hybridization techniques. 2. To compare the cellular immune response of peripheral blood lymphocytes and gastric mucosa lymphocytes to H. pylori antigens in patients with NAG and MAG. 3. To identify the mechanisms by which H. pylori impairs T cell signal transduction and T cell function in patients with H. pylori induced gastritis.